Quaternary salts and method of preparation



United States Patent QUATERNARY SALTS AND METHOD OF PREPARATION DonaldW. Heseltine, Rochester, N. Y., assignor to Eastman'Kodak Company,Rochester, N. Y., a corporation of New Jersey N Drawing. ApplicationDecember 23, 1953, Serial N0. 400,809

10 Claims. 01. 260-240 This invention relates to a method of preparingquaternary salts which are useful in the preparation of sensitizingdyes. More particularly, this invention relates to an improved methodfor making heterocyclic quaternary salts and to new products. I

British Patent 625,907, accepted July 6, 1949, describes a method formaking heterocyclic quaternary salts which are useful in the preparationof photographic sensitizing dyes. However, the intermediates which areobtained according to the process described in this patent are evidentlycontaminated with a material which interferes with certain dyecondensations. For example, the intermediates described in the Britishpatent cannot be condensed with 'so-called ICI intermediates to producedicarbocyanine dyes which can be isolated from the reaction mixture.

1 Accordingly, it would be desirable to have intermediates of thetypedescribed in British Patent 625,907 which were of 'sufiicient purity toundergo condensation's which cannot be undertaken using the Britishpatents intermediates.

It is, therefore, an object of my invention to provide an improvedprocess for preparing intermediates useful in the preparation ofphotographic sensitizing dyes. A further object of my invention is toprovide new intermediates which are useful in the preparation ofphotographic sensitizing dyes. Other objects will become apparent from aconsideration of the following description and examples.

According to my invention, I realize the above objects by condensingtogether a cyclammonium quaternary salt selected from those representedby the following general formula:

C-CH

wherein 'R represents an alkyl group, such as methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, fi-hydroxyethyl, carboxymethyl,carbethoxymethyl, ,8 methdxyethyl, benzyl (phenylmethyl), allyl(vinylmethyl), etc., X represents an anion, such as chloride, bromide,iodide, perchlorate, thiocyanate, acetate, methylsulfate, ethylsulfate,benzenesulfonate, toluenesulfonate, etc., and Z represents thenon-metallic atoms necessary to complete a heterocyclic nucleuscontaining five atoms in the heterocyclic ring, such as those selectedfrom the group consisting of those of the thiazole series (e. g.thiazole, 4- methylthiazole, 5-methylthiazole, 4-phenylthiazole, 5-phenylthiazole, 4,5-dimethylthiazole, 4,5-diphenylthiazole,4-(2-thienyl)thiazole, etc.), those of the benzothiazole series (e. g.benzothiazole, 4-chlorobenzothiazole, 5- chlorobenzothiazole,6-chlorobenzothiazole, 7-chlorobenzothiazole, 4-methylbenzothiazole,S-methylbenzothiazole, G-methylbenzothiazole, S-bromobenzothiazole,fi-bromobenzothiazole, 4 pheny1benzothiazo1e, 5-phenyl-'benzo'thia'zole, 4-r'nethoxyben2othiazole, 5 -methoxybenz othiazole,d-methoxybenzothiazole, 5-iodobenzothiazol, 6-i'odobenzothiazole,4-ethoxybenzothiazole, S-eth'o'xy- "ice - thoxazole, etc.), those of thebenzoselenazole series (e. g. benzoselenazole, S-chlorobenzoselenazole,S-methoxybenzoselenazole, S-hydroxybenzoselenazole,tetrahydrobenzoselenazole, etc.), those of the napthoselenazole series(e. g. u-naphthoselenazole, ,B-naphthoselenazole, etc.), those of thethiazoline series (e. g. thiazoline, 4-methylthiazoline, etc.), with aketone selected from those represented by the following generalformulas:

Bri -CH:

and

2 1120 CHI 0: (BCH3 wherein R represents a carbocyclic aromatic group,such as phenyl, 0-, m,- and p-tolyl, o, m-, and p-chlorophenyl, o, 111-,and p-hydroxyphenyl, o, m-, and p-methoxyphenyl, a-napthy-l, e-naphthyl,2,5-dimethylphenyl, p-dimethylaminophenyl, p diethylaminophenyl, 9phenanthryl, etc., or a heterocyclic radical, such as 2-thienyl, etc.,R2 represents a hydrogen atom or a methyl group, and R3 represents ahydrogen atom, an alkyl group, such as methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, benzyl (phenylmethyl), etc., a monocyclicaryl group,

such as phenyl, o, m-, and p-tolyl, p-methoxyphenyl,

etc., or a furyl group.

The condensation of the compounds represented by Formula I with those ofFormulas II or III can advantageously be accelerated by heating. Theparticular temperature used can be varied, depending on the boilingpoint of the reactants. For example, the reaction can be accelerated bysimply heating the reactants together under reflux. In general, I havefound that a temperature of from about 100 to 200 C. is useful inpracticing my invention. While an inert medium can be employed, ifdesired, there is generally no advantage in using such a medium,inasmuch as such use merely necessitates an additional purification stepin the removal of the solvent.

The intermediates selected from those represented by Formula I abovehave been previously described in the art. See, for example, Brooker andWhite U. S. Patent 2,646,409, issued July 21, 1953; Dent and Brooker U.S. Patent 2,537,880, issued January 9, 1951; and Pittman U. S. Patent2,521,944, issuedSeptember 12, 1950.

The intermediates selected from those represented by Formulas II and IIIabove are also well known in the art.

3 fu1'y1-3-methyl-2-oyclohexene-l-one, 2-cyclohexene-l-one, etc. a

The condensation of the compounds of Formula I with those of Formula IIresults in the formation of intermediates, useful in the preparation ofphotographic sensitizing dyes, having the following general formula:

IV. 'Z\

I) 12-4 b-on zo-om X 1 wherein R, R1, X and Z each have the values givenabove. In lieu of using the quaternary salt represented by Formula I,the corresponding base can be used together with 3-methyl-5-phenyltheappropriate alkyl salt, i. e. R=X, wherein R and X have the values givenabove. thus' formed in situ.

The condensation of the compounds of Formula I with those of Formula IIIresults in the formation of intermediates, useful in the preparation ofphotographic sensitizing dyes, represented by the following generalformula:

The quaternary salt is wherein R, R2, R3, X and Z each have the valuesgiven above.

The intermediates represented by Formula V above are new. Certain of theintermediates represented by Formula IV are also new, such as thosewherein R1 represents a phenanthryl group, a naphthyl group, a 2-thienylgroup, etc.

The following examples willserve to illustrate more fully the mannerwhereby I practice my invention.

1 .3-ethyl-2-(Z-a-naphthylpropenyl) benzothi- Example azolium iodide anddried. After recrystallization from ethyl alcohol,

the yield of purified product was 6.8 g. M. P. 227228 C. dec.

Analysis.-Calcd. for C22H20INS: C, 57.8; H, 4.4; I, 27.8. Found: C,58.0; H, 4.5; I, 28.1.

2.3-ethyl-2- (Z-phenyl) propenylbenzothiawlium-p-toluenesulfonateExample OSOr-CuHP- HIQ) The crude product was 3 ethyl 2methylbenzothiazolium p toluenesulfonate (1 mol., 69.8 g.) andacetophenone (2 mols., 48 g.) were mixed and heated for five minutesunder reflux in a flask fitted with a condenser and a water takeoff. Thehot reaction mixture was poured onto ice (200 g.) and mechanicallystirred and extracted with four 200 ml. portions of ether. The ethersolutions were decanted and the aqueous portion chilled overnight. Thecrude product was filtered off, washed with water and dried. Afterrecrystallization from water, the yield of purified product was 4.85 g.,M. P. 125-126 C. Treatment of the combined aqueous filtrates with sodiumiodide yielded an additional 4.5 g. as the iodide. The combined yield ofproduct was then 11%.

Example 3.3-ethyl-2-(1,5,5-trimethyl-3-cycl0hexenylidene)methylbenzothiazolium iodide 3 ethyl 2,- methylbenzothiazolium ptoluenesulfonate (1 mol., 34.9 g.) and isophorone (2 mols.,'27.6 g.)were mixed in a 500 ml. flask fitted with an air condenser and a watertake-off. The reaction mixture was heated in an oil bath at 140 C. for16 hours and then poured hot into a 1500 ml. beaker and mechanicallystirred with 200 ml. water. The mixture was extracted with five 200 ml.portions of ether and then the aqueous portion was treated with anaqueous solution of sodium iodide (15 g. in water (50 ml.)). Afterchilling over-. night, the crude product was filtered ofi, thoroughlywashed with water and dried. After recrystallization from ethyl alcohol,the yield of purified product was 14.7 g. (35%), M. P. 233-234 C. dec.

Example 4.3-ethyl-2- [2-(2-thienyl) propenyl] benzorhiazoliump-toluenesulfonate 3 ethyl 2 methylbenzothiazolium p toluenesulfonate(34.9 g., 1 mol.) and methyl-Z-thienylketone (13.9 g., 1 mol. plus 10%)were mixed and heated in an oil bath at -135 C. for16 hours. Thereaction mixture was then poured into water (100 ml.) with stirring. Themixture was then stirred and extracted with four 200 ml. portions ofether. The. product crystallized from the aqueous portion, was filteredoff, washed with water and ether, and dried. After tworecrystallizations from methyl alcohol, the yield of pure product was5.2 grams (11%). M. P. -1 C. dec.

Example 5 .--3-ethyl-2- [2-( Z-thienyl) propertyl] naphtha [1,2]-thiaz0liu m iodide I 02H; I

danger! G the oil bath at 130-135" C. for 16 hours in a flask fittedwith a Water take-off and an air condenser. The reaction mixture wasthen stirred with water (500 ml.) and four 500 ml. portions of ether.The ether was decanted and steam passed intothe mixture until the totalvolume was 2500 ml. The aqueous solution was then stirred with Super Cel(a diatomaceous earth) g.), filtered, and treated with sodium iodideg.). After chilling overnight, the crude product was filtered 01f,boiled with water (250 1111.), filtered hot and dried. The yield ofcrude product was 4.6 grams (10%). After two recrystallizations frommethyl alcohol, the yield of pure product was 5%. M. P. 215-216 C. dec.

Example 6 .3-ethyl-2- [2- p-dimethylaminophenyl propenyl]benzothiazolium iodide 3 ethyl 2 methylbenzothiazolium ptoluenesulfonate (34.9 g., 1 mol.) and p-dimethylaminoacetophenone (16.3g., 1 mol.) were mixed and heated on an oil bath at 135-140 C. for 24hours. The reaction mixture was poured into water (800 ml.) andmechanically stirred with 400 ml. portions of ether. A fifth portion ofether was added and the stirring continued until the sticky solid becamecrystalline. The aqueous portion was then filtered and 6.1 g. of theproduct isolated as the p-toluenesulfonate. Treatment of the aqueousfiltrate with sodium iodide (5 g.) yielded an additional 2.1 g. as theiodide. After two recrystallizations from methyl alcohol, the iodide hadM. P. 21819 C. dec.

Example 7 .3-ethyl-2- [2- (2,5 -dimetl1ylphenyl propenylbenzothz'azolium iodide Example 8.3-ethyl-2-[2-(Q-phenanthryl) propenyl]benzothiozolium iodide 3 ethyl 2 methylbenzothiazolium ptoluenesulfonate (34.9 g., 1 mol.) and 9 -acetyl'phenanthrene (22.0 g.,1 mol.) were mixed and heated on an oil bath at 6 -l40 C. for 2 days.The reaction mixture was pouredinto water (800 ml.) and stirred withfour 400 m1. portions of ether. The ether was decanted and the aqueousportion treated with sodium iodide (20 g.) and chilled overnight. Thewater was decanted and the residue stirred with ethyl aclohol untilcrystalline, chilled, and filtered. The yield of product was 12.7 g.(25% M, P. 110-111 C. Example 91-ethyl-Z-(2-p-hydroxyplzenyl)propertylnaplzrho 1 ,2] -thiazolium iodide/CCH=COH| l 01H: I

1 ethyl 2 methylnapthoi1,2]thiazoliump-toluenesulfonate (39.9 g., 1mol.) and p-hydroxyacetophenone (27.2 g., 1 mol. plus 100%) were mixedand heated on the oil bath at 165-170 C. for 24 hours. The crudereaction mixture was poured into a 2000 ml. beaker and mechanicallystirred with water (400 ml. and four 500 ml. portions of ether. Theether and water solutions were decanted and the residue extracted withboiling water (3 liters). The aqueous solution was filtered and treatedwith stirring and with sodium iodide (10 g.) and then chilled overnight.The crude product was filtered off, boiled with 600 ml. water andfiltered hot, washed with water and ether and dried. The yield after tworecrystallizations from methyl alcohol with 2.05 g. M. P. 247- 8 C. dec.

Example 10.] methyl 2 [2 (1 naphthyDpropenyl] naphtha [1,2] thz'azoliumiodide 1,2-dimethylnaphtho[ 1,2] thiazolium p-toluenesulfonate (38.5 g.,1 mol.) and l-acetonaphthone (18.7 g., 1 mol. plus 10%) were mixed andheated on the oil bath at 145 C. for 2 days. The crude reaction mixturewas poured into water (1000 ml.) and stirred with four 500 ml. portionsof ether. The ether solutions were discarded and the aqueous portionstirred with sodium iodide (20 g.) The Water was decanted and theresidue boiled with two 500 ml. portions of water and the waterdecanted. The residue was then dissolved in boiling acetone, filtered,and chilled overnight. The product was then filtered ofi, washed withacetone and dried. The yield was 5.1 g. (10.4% M. P. 172-4 C. dec.

Example 11.5 chloro 3 ethyl 2 (1,5,5 trimethyl- 3 cyclohexenylidene)methylbenzothiazolium p toluenesulfonate OSOr-CoH4-CH:(D)S-chloro-3-ethyl-2-rnethylbenzothiazolium p-toluenesulfonate (38.4 g., 1mol.) and isophorone (27.6 g., 1 mol. plus 100%) were mixed and heatedon the oil bath at Example 12. 3 ethyl 2 1,5,5 tn'methyl 3cyclohexenylidene) methylbenzoxazolium iodide CH: CH:

a C-CH:

115 I Z-methylbenzoxazole (13.3 g., 1 mol.), ethyl p-toluenesulfonate(20.0 g., 1 mol.) and isophorone (27.6 g., lmol. plus 100%) were mixedand heated on the oil bath at 135140 C. for 16 hours. The reactionmixture was then poured into water (600 ml.) and mechanically stirredwith four 500 ml. portions of ether. An additional 500 ml. of ether wasadded and the mixture stirred with sodium iodide (20 g.). After chillingfor several days, the crystalline product was filtered off, stirred witha little acetone, chilled, filtered, and dried. The yield of product was4.3 g. (10.4%). M. P. 2l7--18 C. dec.

.Example l3.3 ethyl 2 (1,5,5 trimethyl 3 cyclohexenylidene)methylbenzoselenazolium iodide 2-methylbenzoselenazole (19.6 g., 1 mol.)and diethylsulfate (15.4 g., 1 mol.) were mixed and heated at 70 C. onthe oil bath for 24'hours. Isophorone (27.6 g., 1 mol. plus 100%) wasthen added and the mixture heated at 135140 C. for 16 hours. Thereaction mixture was poured into water (800 ml.) and stirred with four500 ml. portions of ether. The ether was decanted and the aqueousportion treated with sodium iodide (20 g.). The water was decanted andthe residue washed with water, boiled with acetone, chilled, filtered,and dried. The yield of product was 8.5 g. (18%). M. P. 223-4 C. dec.

Example l4.2 (1,5 dimethyl 3 cycl0hexenylidene)- methyl 3 7 ethylbenzothiazolium iodide 3-ethyl 2 methylbenzothiazolium p toluenesulfonate(34.9 g., 1 mol.) and 3,5-dimethyl-2-cyclohexene-l-one- 8 ethyl alcohol,the yield of product was 6.5 g. (16%). M. P. 236-7 C. dec. Example15.1-ethyl-2- (1,5,5-trimethyl-.i-cyclohexenylidene)methylnaphtho [1,2]thiazolium iodide l-ethyl-Z-mathylnaphtho [1,2lthiazoliump-toluenesulfonate (39.9 g., 1 mol.) and isophorone (27.6 g., 1 mol.plus were mixed and heated in an oil bath at C. for 24 hours. Thereaction mixture was poured into a beaker and mechanically stirred withwater (400 ml.) and five 400 ml. portions of ether. The ether and watersolutions were decanted and the residue extracted with boiling water(300 ml.). The aqueous solution was then filtered, stirred with sodiumiodide and chilled overnight. The crude product was filtered ofi, washedwith water, stirred with acetone, filtered, and dried. Afterrecrystallization from ethyl alcohol, the yield was 10.8 g. (23%). M. P.208-9 C. dec.

Example I 6 .1 -ethyl-2-( I ,5 ,5 -trir rzethylcyclohexenylidene)methylnaphtho [2,1 l thiazolium iodide CH3 CB:

2-methylnaphtho[2,1]thiazole (39.8 g., 1 mol.), ethyl p-toluenesulfonate(40 g., 1 mol.) andisophorone (30.3 g., 1 mol. plus 10%) Were mixed in a500 ml. flask fitted with a water take-off and an air condenser. Thereaction mixture was heated in an oil bath at l35140 C. for 3 days. Thereaction mixture was then poured into water (800 ml.) and stirred andextracted with four 800 ml. portions of ether. The ether solutions werediscarded and the aqueous layer decanted. The residue was then extractedwith boiling water (800 ml.) and the aqueous solutions combined,saturated with ammonium chloride and chilled overnight. The product wasfiltered, dissolved in water (100 ml.) and converted to the bromide bythe addition of sodium bromide (10 g.). The crude bromide was filteredoff, washed with acetone and dried. Yield 6.5 g. An additional 7.3 g.was isolated as the iodide by treating the combined filtrates withsodium iodide (20 g.). The crude iodide was boiled with two 400 ml.portions of Water, washed with acetone and dried. The combined yield was15.3% and the iodide after recrystallization from methyl alcohol had M.P. 252-3 C. dec.

Operating in a similar manner, other cyclammonium quaternary saltsselected from those represented by Formulas II and III. As noted above,the resulting intermediates represented by Formulas IV and V canadvantageously be employed through condensation with ICI intermediatesor Dains intermediates to produce polymethine dyes useful in alteringthe sensitivity of photographic silver halide emulsions. The preparationof such dyes is described in my copending application Serial No. 400,810filed on even date herewith (now U. S. Patent 2,734,900, issued February14, 1956).

What I claim as my invention and desired secured by Letters Patent ofthe United States is:

1. A process for making heterocyclic compounds comprising reacting acompound selected from those represented by the following generalformula:

I RN21CH3 wherein R represents an alkyl group, X represents an anion,and Z represents the non-metallic atoms necessary to complete aheterocyclic nucleus selected from the group consisting of those of thethiazole series, those of the benzothiazole series, those of thenaphthothiazole series, those of the benzoxazole series, those of thenaphthoxazole series, those of the benzoselenazole series, those of thenaphthoselenazole series, and those of the thiazoline series with aketone selected from those represented by the following general formula:

wherein R1 represents a member selected from the group consisting of aZ-thienyl group and an aromatic carbocyclic group containing from 6 to14 carbon atoms.

2. A process for preparing heterocyclic compounds comprising reacting acompound selected from those represented by the following generalformula:

wherein R represents an alkyl group having the formula CnHzn+1 wherein nrepresents a positive integer of from 1 to 4, X represents an anion, andZ represents the nonmetallic atoms necessary to complete a heterocyclicnucleus of the benzothiazole series, with a ketone selected from thoserepresented by the following general formula:

wherein R represents an alkyl group having the formula CnH2n+1 wherein nrepresents a positive integer of from 1 to 4, X represents an anion, andZ represents the nonmetallic atoms necessary to complete a heterocyclicnucleus of the naphthothiazole series, with a ketone selected from thoserepresented by the following general formula:

ng-ii-ont wherein R1 represents an aromatic carbocyclic group containingfrom 6 to 14 carbon atoms.

4. A process for preparing heterocyclic compounds comprising reacting acompound selected from those represented by the following generalformula:

b-ou,

wherein R represents an alkyl group having the formula cnH2n+1 wherein nrepresents a positive integer of from 1 to 4, X represents an anion andZ represents the nonmetallic atoms necessary to complete a heterocyclicnucleus of the naphthothiazole series, with p-hydroxyacetophenone.

6. A process comprising reacting3-ethyl-2-methyl-benzothiazolium-p-toluenesulfonate together withacetophenone.

7. A process comprising reacting l-ethyl-Z-methylnaphtho [1,2]thiazolium p-toluenesulfonate with p-hydroxyacetophenone.

8. A process comprising reacting 3-ethyl-2-methylbenzothiazoliump-toluenesulfonate with methyl-Z-thienyl ketone.

9. A process comprising reacting l-ethyl-Z-methyl naphtho [1,2]thiazolium p-toluenesulfonate with methyl- Z-thienyl ketone.

10. A process comprising reacting 3-ethyl-2-methy1benzothiazoliump-toluenesulfonate with 9-acetylphenanthrene.

References Cited in the file of this patent UNITED STATES PATENTS2,028,141 Ackermann Ian. 21, 1936 2,107,379 Koslowsky Feb. 8, 19382,126,078 Zeh Aug. 9, 1938 2,231,659 Brooker Feb. 11, 1941 2,450,400Thompson Sept. 28, 1948 2,541,015 Van Lare et a1. Feb. 13, 1951 FOREIGNPATENTS 625,907 Great Britain July 6, 1949 OTHER REFERENCES Skraup etal.: Ber. Deut. Chem., vol. 59B, p. 1014 (1926).

Naiman et al.: IACS, vol. 57, pp. 1660-3 (1935).

Brown et al.: J. Org. Chem., vol. 15, pp. 174-6 (1950).

Smet et al.: Chem. Abst., vol. 45, col. 607 (1951).

1. A PROCESS FOR MAKING HETEROCYCLIC COMPOUNDS COMPRISING REACTING ACOMPOUND SELECTED FROM THOSE REPRESENTED BY THE FOLLOWING GENERALFORMULA: